Cambios en Mecánica Respiratoria en Usuarios Pediátricos en Ventilación Mecánica Post Cirugía de Cardiopatía Congénita Sometidos a Kinesiología Respiratoria versus Succión Endotraqueal. Revisión Estructurada / Changes in Respiratory Mechanics in Pediatric Users on Mechanical Ventilation Post Congenital Heart Disease Surgery Undergoing Respiratory Kinesiology versus Endotracheal Suction. Structured Review

Introducción. Las cardiopatías congénitas (CC) en Chile corresponden a la segunda causa de muerte en menores de 1 año, requiriendo cirugías paliativas y/o correctivas el 65% de estas. En el post operatorio frecuentemente se utiliza ventilación mecánica invasiva (VM) y succión endotraqueal (SET) para remover secreciones. Sin embargo, la kinesiología respiratoria (KTR) ha mostrado mejoras significativas en la distensibilidad toracopulmonar (Cest) y resistencia de vía aérea (Rva) en otros grupos de usuarios pediátricos y adultos en VM. Objetivo. Comparar los cambios en la Cest y Rva en usuarios pediátricos en VM post cirugía de cardiopatía congénita (CCC) sometidos a KTR versus SET exclusiva. Métodos. Revisión sistemática de estudios publicados en bases de datos PUBMED, PeDro, Scielo y Google Scholar que comparan el uso de KTR ó SET sobre los cambios en mecánica ventilatoria en usuarios pediátricos en VM post cirugía de cardiopatía congénita, limitados a inglés, español y portugués, excluyendo a sujetos con traqueostomía o con oxigenación por membrana extracorpórea. Se utilizó guía PRISMA para la selección de artículos. Se revisaron 397 artículos y se seleccionó 1 artículo extra de los artículos sugeridos. Se eliminó 1 artículo por duplicidad. Por títulos y resúmenes se seleccionaron 2 artículos, los cuales al leer el texto completo fueron retirados debido a que la población no correspondía a cardiópatas. Resultados. El final de artículos seleccionados fue de 0 artículos, debido a lo cual se removió el operador Booleano "NOT", y se removió la población de cardiopatías. De este modo quedaron 2 artículos seleccionados para la revisión cualitativa final donde se compara KTR versus SET, y KTR en kinesiólogos especialistas y no especialistas, mostrando ambos aumento en la Cest y disminución de la Rva a favor de la KTR, hasta los 30 minutos post intervención. Conclusiones. No se encontraron artículos que demuestren cambios en Cest y Rva con el uso de KTR + SET versus SET exclusiva, en usuarios pediátricos ventilados posterior a CCC. Con la remoción de filtros seleccionamos 2 artículos que demuestran aumento de Cest y disminución de Rva en sujetos pediátricos en VM, uno comparando con SET, y por grupos de especialistas y no especialistas en respiratorio. Se sugieren estudios primarios para evaluar los efectos de esta intervención en esta población.

Introduction. Congenital heart diseases (CHD) are the second general cause for children death under 1 year. In Chile, approximately 65% CHD need surgery, could was palliative or corrective. In the postoperative period, invasive mechanical ventilation (MV) is frequently used as a life support method, but it is associated with complications. Tracheal suction (SET) is regularly used to remove secretions; however, respiratory chest physiotherapy (KTR) has shown significant improvements in thoraco-pulmonary compliance and airway resistance in other groups of pediatrics and adult's users in MV. Objetive. to compare changes in thoraco-pulmonary compliance and airway resistance in pediatric subjects under mechanical ventilation after congenital heart disease surgery comparing chest physiotherapy and exclusive tracheal suction. Methods. systematic review of studies published in PUBMED, PeDro, Scielo and Google Scholar databases who compares KTR or SET use on changes in ventilatory mechanics in pediatric users under MV after congenital heart disease surgery, limited to English, Spanish and Portuguese languages, excluding user with tracheostomy or extracorporeal membrane of oxygenation. It was use the PRISMA guide to articles selection. A search was carried out, with a total of 397 articles reviewed (English: PubMed = 3, PeDro = 8, Scholar = 383; Spanish: Scholar = 3, Scielo = 0; and Portuguese: Scielo = 0). One extra article was selected from the suggested articles, and 1 article was eliminated due to duplication. By titles and abstracts, 2 articles were selected, but the population did not correspond to heart disease. Results. the final selected articles were 0 articles. By this reason, it were removed: Boolean operator "NOT", and congenital heart disease population. Thus, 2 articles were selected for the final qualitative review where it was compares KTR versus SET, and KTR by specialist and non-specialist. Both articles shown improvement in compliance and resistance until 30 minutes post intervention. The CC population was in a 40 to 60% range in both studies. Conclusions. it was no found articles that demonstrate changes in compliance and resistance in the airway with the use of KTR + SET versus exclusive SET in pediatric users after CCC connected to MV. After filter remotion, we found 2 studies shown improves in increase compliance and reduce resistance in pediatric user in MV, ones comparing with SET, and the other one comparing between specialists in respiratory pediatric physiotherapy and not specialists. It suggests to made primary clinical studies about this intervention in CC population.

Chronic restraint stress produces sex-specific behavioral and molecular outcomes in the dorsal and ventral rat hippocampus.

Stress-related disorders display differences at multiple levels according to sex. While most studies have been conducted in male rodents, less is known about comparable outcomes in females. In this study, we found that the chronic restraint stress model (2.5 h/day for 14 days) triggers different somatic responses in male and female adult rats. Chronic restraint produced a loss in sucrose preference and novel location preference in male rats. However, chronic restraint failed to produce loss of sucrose preference in females, while it improved spatial performance. We then characterized the molecular responses associated with these behaviors in the hippocampus, comparing the dorsal and ventral poles. Notably, sex- and hippocampal pole-specific transcriptional signatures were observed, along with a significant concordance between the female ventral and male dorsal profiles. Functional enrichment analysis revealed both shared and specific terms associated with each pole and sex. By looking into signaling pathways that were associated with these terms, we found an ample array of sex differences in the dorsal and, to a lesser extent, in the ventral hippocampus. These differences were mainly present in synaptic TrkB signaling, Akt pathway, and glutamatergic receptors. Unexpectedly, the effects of stress on these pathways were rather minimal and mostly dissociated from the sex-specific behavioral outcomes. Our study suggests that female rats are resilient and males susceptible to the restraint stress exposure in the sucrose preference and object location tests, while the activity of canonical signaling pathways is primarily determined by sex rather than stress in the dorsal and ventral hippocampus.

Sex-Dependent Changes of miRNA Levels in the Hippocampus of Adrenalectomized Rats Following Acute Corticosterone Administration.

We explored sex-biased effects of the primary stress glucocorticoid hormone corticosterone on the miRNA expression profile in the rat hippocampus. Adult adrenalectomized (ADX) female and male rats received a single corticosterone (10 mg/kg) or vehicle injection, and after 6 h, hippocampi were collected for miRNA, mRNA, and Western blot analyses. miRNA profiling microarrays showed a basal sex-biased miRNA profile in ADX rat hippocampi. Additionally, acute corticosterone administration triggered a sex-biased differential expression of miRNAs derived from genes located in several chromosomes and clusters on the X and 6 chromosomes. Putative promoter analysis unveiled that most corticosterone-responsive miRNA genes contained motifs for either direct or indirect glucocorticoid actions in both sexes. The evaluation of transcription factors indicated that almost 50% of miRNA genes sensitive to corticosterone in both sexes was under glucocorticoid receptor regulation. Transcription factor-miRNA regulatory network analyses identified several transcription factors that regulate, activate, or repress miRNA expression. Validated target mRNA analysis of corticosterone-responsive miRNAs showed a more complex miRNA-mRNA interaction network in males compared to females. Enrichment analysis revealed that several hippocampal-relevant pathways were affected in both sexes, such as neurogenesis and neurotrophin signaling. The evaluation of selected miRNA targets from these pathways displayed a strong sex difference in the hippocampus of ADX-vehicle rats. Corticosterone treatment did not change the levels of the miRNA targets and their corresponding tested proteins. Our data indicate that corticosterone exerts a sex-biased effect on hippocampal miRNA expression, which may engage in sculpting the basal sex differences observed at higher levels of hippocampal functioning.

Electrical cortical stimulation can impair production of the alphabet without impairing counting.

Neurosurgery has the potential to cure patients with drug-resistant focal epilepsy, but carries the risk of permanent language impairment when surgery involves the dominant hemisphere of the brain. This risk can be estimated and minimized using electrical stimulation mapping (ESM), which uses cognitive and linguistic tasks during cortical ESM to differentiate "eloquent" and "resectable" areas in the brain. One such task, counting, is often used to screen and characterize language during ESM in patients whose language abilities are limited. Here we report a patient with drug-resistant epilepsy arising from the language-dominant hemisphere using fMRI. Our patient experienced loss of the ability to recite or write the alphabet, but not to count, during ESM of the dominant left posterior superior temporal gyrus. This selective impairment extended to both spoken and written production. We suggest the need for caution when using counting as a sole means to screen language function and as a method of testing low functioning patients using ESM.

Blue light absorbing pigment in Streptococcus agalactiae does not potentiate the antimicrobial effect of pulsed 450 nm light.

INTRODUCTION: Recently, it was shown that Group B Streptococcus (GBS) COH1 strain, which has granadaene-an endogenous chromophore known to absorb blue light-is not susceptible to 450 nm pulsed blue light (PBL) inactivation unless the bacterium is co-cultured with exogenous porphyrin. PURPOSE: To confirm or refute the finding, we studied the effect of blue light on NCTC, another strain of GBS with more granadaene than COH1, to determine if the abundance of granadaene-and by implication more absorption of blue light-fosters GBS susceptibility to PBL. METHODS: We irradiated cultures of the bacterium with or without protoporphyrin, coproporphyrin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD) or NADH. After 24-h incubation, bacterial colonies were enumerated, log10 CFU/mL computed, and descriptive and inferential data analyzed and compared. RESULTS: (1) The rich amount of granadaene in NCTC did not enhance its susceptibility to antimicrobial pulsed blue light (PBL). (2) Adding exogenous porphyrin fostered NCTC susceptibility to irradiation, resulting in 100% bacterial suppression. (3) Exogenous FMN or FAD, which strongly absorb 450 nm light, did not promote the antimicrobial effect of PBL, neither did exogenous NAD or NADH, two weak blue light-absorbing photosensitizers. CONCLUSION: These results strengthen our previous assertion that an endogenous chromophore with the capacity to absorb and transform light energy into a biochemical process that engenders bacterial cell death, is essential for 450 nm PBL to suppress GBS.

Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats.

Several lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions. 89 adult male Sprague-Dawley rats received intraperitoneal fasudil injections (10 mg/kg/day) or saline vehicle for 18 days. Some of these animals were daily restraint-stressed from day 5-18 (2.5 h/day). 24 hr after treatments, rats were either evaluated for behavioral tests (active avoidance, anxiety-like behavior and object location) or euthanized for western blot analyses of hippocampal whole extract and synaptoneurosome-enriched fractions. We report that fasudil prevents stress-induced impairments in active avoidance, anxiety-like behavior and novel location preference, with no effect in unstressed rats. Chronic stress reduced phosphorylations of ERK-2 and CREB, and decreased levels of GluA1 and GluN2A in whole hippocampus, without any effect of fasudil. However, fasudil decreased synaptic GluA1 Ser831 phosphorylation in stressed animals. Additionally, fasudil prevented stress-decreased phosphorylation of GSK-3ß at Ser9, in parallel with an activation of the mTORC1/4E-BP1 axis, both in hippocampal synaptoneurosomes, suggesting the activation of the AKT pathway. Our study provides evidence that chronic fasudil treatment prevents chronic stress-altered behaviors, which correlated with molecular modifications of antidepressant-relevant signaling pathways in hippocampal synaptoneurosomes.

"Library and Information Science" Literature in Web of Science: What a Decade Tells Us About Scholarly Collaboration in the Field (2007-2016) / Literatura sobre "Bibliotecología y Ciencias de la Información" en Web of Science: Qué nos dice una década sobre la colaboración académica en el campo (2007-2016)

Abstract Ensuring access to published research is increasingly important for demonstrating research impact, supporting wide readership, creating interest in collaboration, and making way for funding opportunities. This article provides a bibliometric analysis of publications from 2007-2016 in the Web of Science (WOS) database to update understanding of recent international library science research as a means of discussing research impact and scientific collaboration. The methodology is a descriptive analysis of publications retrieved from the WOS database using keywords "library science" and WOS-generated subject descriptor "Information Science & Library Science." Analysis focused on descriptive data related to our research questions including representation of countries, languages, and journals. The findings reveal that most publications are published by researchers with institutional affiliations in the United States and in English. Library and information science research continues to be strong in collaboration, but international and interdisciplinary collaborations are still low in this sample. The dataset reflects that co- and multi-authored publications have the highest WOS citation counts, reinforcing the value of scholarly collaboration. This research provides a baseline to chart future growth in Library Science research publications and collaborations.

Resumen Asegurar el acceso a la investigación publicada es cada vez más importante para demostrar el impacto de la investigación, apoyar un amplio número de lectores, crear interés en la colaboración y dar paso a oportunidades de financiamiento. Este artículo proporciona un análisis bibliométrico de las publicaciones 2007-2016 en la base de datos de Web of Science (WOS) para actualizar la comprensión de la internacionalización reciente de la investigación en el campo de la bibliotecología como medio para discutir el impacto de la investigación y la colaboración científica. La metodología es un análisis descriptivo de las publicaciones recuperadas de la base de datos de WOS, utilizando las palabras clave "Bibliotecología" y el encabezado de materia "Ciencia de la información y biblitecología" generado por WOS. El análisis se centró en datos descriptivos relacionados con las preguntas de investigación, incluida la representación de países, idiomas y revistas, así como patrones de autoría con colaboraciones internacionales, nacionales, intrainstitucionales e interdisciplinarias y recuentos de citas. Los hallazgos revelan que la mayoría de los artículos son publicados en inglés, por investigadores con afiliaciones institucionales en los Estados Unidos. Las investigaciones sobre Bibliotecología y Ciencias de la Información continúan siendo sólidas en colaboración, pero las colaboraciones internacionales e interdisciplinarias aún son bajas en esta muestra. El conjunto de datos refleja que las publicaciones de coautoría y de múltiples autores tienen el mayor número de citas de WOS, lo que refuerza el valor de la colaboración académica. Esta investigación proporciona una base para registrar el futuro crecimiento de las publicaciones y colaboraciones de investigación en Bibliotecología.

The importance of porphyrins in blue light suppression of Streptococcus agalactiae.

It is well documented that blue light absorption by bacterial chromophores triggers downstream production of reactive oxygen species (ROS), which in turn results in bacterial cell death. To elucidate the importance of chromophores in the bactericidal effect of blue light, and to determine whether blue light absorption per se or the presence of porphyrins known to engender ROS is crucial in blue light treatment, we studied the effect of 450 nm pulsed light on Streptococcus agalactiae, also known as Group B Streptococcus (GBS) strain COH1. GBS does not synthesize porphyrins but has a blue light-absorbing chromophore, granadaene. We irradiated planktonic cultures of GBS with or without exogenous chromophore supplementation using either protoporphyrin IX (PPIX), coproporphyrin III (CPIII), Nicotinamide adenine dinucleotide (NAD), reduced nicotinamide adenine dinucleotide (NADH), Flavin adenine dinucleotide (FAD), or Flavin mononucleotide (FMN). Quantification of surviving bacterial colonies, presented as percent survival and CFU/mL (log10), showed that (1) 450 nm blue light does not suppress the growth of GBS, even though its endogenous chromophore, granadaene, absorbs light in the 450 nm spectrum. (2) The addition of either of the two exogenous porphyrins, PPIX or CPIII, significantly suppressed GBS, indicating the importance of porphyrins in the antimicrobial action of blue light. (3) Adding exogenous FMN or FAD, two known absorbers of 450 nm light, minimally potentiated the bactericidal effect of blue light, again confirming that mere absorption of blue light by chromophores does not necessarily result in bacterial suppression. (4) Irradiation of GBS with or without NAD+ or NADH supplementation-two weak absorbers of 450 nm light-minimally suppressed GBS, indicating that a blue light-absorbing chromophore is essential for the bactericidal action of blue light. (5) Collectively, these findings show that in addition to the presence of a blue light-absorbing chromophore in bacteria, a chromophore with the right metabolic machinery and biochemical structure, capable of producing ROS, is necessary for 450 nm blue light to suppress GBS.

Hippocampal Memory Recovery After Acute Stress: A Behavioral, Morphological and Molecular Study.

Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated-at the same time-the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. The aim of our study was to take a multidimensional approach to investigate concomitant behavioral, morphological and molecular changes induced by a single restraint stress exposure (2.5 h) and a recovery period of 6 and 24 h in rats. We found that acute stress elicited a reduced preference to explore an object placed in a novel position (a hippocampal-dependent task). These changes were accompanied by increased activity of LIM kinase I (LIMK; an actin-remodeling protein) and increased levels of NR2A subunits of NMDA receptors. After 6 h of recovery from stress, rats showed similar preference to explore an object placed in a novel or familiar position, but density of immature spines increased in secondary CA1 apical dendrites, along with a transient rise in GluA2 AMPA receptor subunits. After 24 h of recovery from stress, the animals showed a preference to explore an object placed in a novel position, which was accompanied by a normalization of NMDA and AMPA receptor subunits to control values. Our data suggest that acute stress produces reversible molecular and behavioral changes 24 h after stress, allowing a full reestablishment of hippocampal-related memory. Further studies need to be conducted to deepen our understanding of these changes and their reciprocal interactions.Adaptive stress responses are a promising avenue to develop interventions aiming at restoring hippocampal function impaired by repetitive stress exposure.

MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology.

Studies conducted in rodents subjected to chronic stress and some observations in humans after psychosocial stress, have allowed to establish a link between stress and the susceptibility to many complex diseases, including mood disorders. The studies in rodents have revealed that chronic exposure to stress negatively affects synaptic plasticity by triggering changes in the production of trophic factors, subunit levels of glutamate ionotropic receptors, neuron morphology, and neurogenesis in the adult hippocampus. These modifications may account for the impairment in learning and memory processes observed in chronically stressed animals. It is plausible then, that stress modifies the interplay between signal transduction cascades and gene expression regulation in the hippocampus, therefore leading to altered neuroplasticity and functioning of neural circuits. Considering that miRNAs play an important role in post-transcriptional-regulation of gene expression and participate in several hippocampus-dependent functions; we evaluated the consequences of chronic stress on the expression of miRNAs in dorsal (anterior) portion of the hippocampus, which participates in memory formation in rodents. Here, we show that male rats exposed to daily restraint stress (2.5 h/day) during 7 and 14 days display a differential profile of miRNA levels in dorsal hippocampus and remarkably, we found that some of these miRNAs belong to the miR-379-410 cluster. We confirmed a rise in miR-92a and miR-485 levels after 14 days of stress by qPCR, an effect that was not mimicked by chronic administration of corticosterone (14 days). Our in silico study identified the top-10 biological functions influenced by miR-92a, nine of which were shared with miR-485: Nervous system development and function, Tissue development, Behavior, Embryonic development, Organ development, Organismal development, Organismal survival, Tissue morphology, and Organ morphology. Furthermore, our in silico study provided a landscape of potential miRNA-92a and miR-485 targets, along with relevant canonical pathways related to axonal guidance signaling and cAMP signaling, which may influence the functioning of several neuroplastic substrates in dorsal hippocampus. Additionally, the combined effect of miR-92a and miR-485 on transcription factors, along with histone-modifying enzymes, may have a functional relevance by producing changes in gene regulatory networks that modify the neuroplastic capacity of the adult dorsal hippocampus under stress.

Matrix Metalloproteinase 9 Displays a Particular Time Response to Acute Stress: Variation in Its Levels and Activity Distribution in Rat Hippocampus.

A single stress exposure facilitates memory formation through neuroplastic processes that reshape excitatory synapses in the hippocampus, probably requiring changes in extracellular matrix components. We tested the hypothesis that matrix metalloproteinase 9 (MMP-9), an enzyme that degrades components of extracellular matrix and synaptic proteins such as ß-dystroglycan (ß-DG43), changes their activity and distribution in rat hippocampus during the acute stress response. After 2.5 h of restraint stress, we found (i) increased MMP-9 levels and potential activity in whole hippocampal extracts, accompanied by ß-DG43 cleavage, and (ii) a significant enhancement of MMP-9 immunoreactivity in dendritic fields such as stratum radiatum and the molecular layer of hippocampus. After 24 h of stress, we found that (i) MMP-9 net activity rises at somatic field, i.e., stratum pyramidale and granule cell layers, and also at synaptic field, mainly stratum radiatum and the molecular layer of hippocampus, and (ii) hippocampal synaptoneurosome fractions are enriched with MMP-9, without variation of its potential enzymatic activity, in accordance with the constant level of cleaved ß-DG43. These findings indicate that stress triggers a peculiar timing response in the MMP-9 levels, net activity, and subcellular distribution in the hippocampus, suggesting its involvement in the processing of substrates during the stress response.

Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats.

Previous studies in rats have demonstrated that chronic restraint stress triggers anhedonia, depressive-like behaviors, anxiety and a reduction in dendritic spine density in hippocampal neurons. In this study, we compared the effect of repeated stress on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subunits in dorsal and ventral hippocampus (VH). Adult male Sprague-Dawley rats were randomly divided into control and stressed groups, and were daily restrained in their motion (2.5 h/day) during 14 days. We found that chronic stress promotes an increase in c-Fos mRNA levels in both hippocampal areas, although it was observed a reduction in the immunoreactivity at pyramidal cell layer. Furthermore, Arc mRNAs levels were increased in both dorsal and VH, accompanied by an increase in Arc immunoreactivity in dendritic hippocampal layers. Furthermore, stress triggered a reduction in PSD-95 and NR1 protein levels in whole extract of dorsal and VH. Moreover, a reduction in NR2A/NR2B ratio was observed only in dorsal pole. In synaptosomal fractions, we detected a rise in NR1 in dorsal hippocampus (DH). By indirect immunofluorescence we found that NR1 subunits rise, especially in neuropil areas of dorsal, but not VH. In relation to AMPA receptor (AMPAR) subunits, chronic stress did not trigger any change, either in dorsal or ventral hippocampal areas. These data suggest that DH is more sensitive than VH to chronic stress exposure, mainly altering the expression of NMDA receptor (NMDAR) subunits, and probably favors changes in the configuration of this receptor that may influence the function of this area.

Metastasis pulmonares tardías de carcinoma adenoideo quístico de la glandula de bartolino / Late lung metastases of cystic adenoid carcinoma of the bartolino gland

El carcinoma adenoideo quístico de la glándula de Bartolino (GB) es una entidad infrecuente, de crecimiento lento y comportamiento agresivo con alta recurrencia local y metástasis. Presentamos el caso de una paciente de 48 años, con antecedente de tratamiento quirúrgico de un absceso Bartolino derecho. La biopsia demostró un carcinoma adenoideo quístico (CAQ) de la GB, por lo que se realizó hemivulvectomía radical derecha y linfadenectomía inguinofemoral. El resultado de la biopsia mostró 4 ganglios positivos de 12 y margen lateral positivo a menos de 2 mm. Por lo que se realizó adyuvancia con radioterapia. La paciente no se presenta a su control y acude luego de tres años por dolor urente desde cadera izquierda hacia rodilla y cara lateral de la pierna y pie. Se realiza cintigrama óseo que muestra lesión osteoblástica sacroilíaca izquierda de 2 cm, por lo que se completó estudio de diseminación con tomografía computada de tórax, abdomen y pelvis con contraste que evidenció múltiples lesiones nodulares pulmonares bilaterales de distribución generalizada en parénquima central, periférico y subpleurales. Se deriva al Instituto Nacional del Tórax, completando estudio preoperatorio y se realizó una biopsia quirúrgica por video toracoscopía resecando un nódulo subpleural, el informe histológico señaló una metástasis de CAQ concordante con primario en GB. La paciente fue presentada en el comité oncológico y se indicó radioterapia paliativa a lesión sacroilíaca y control clínico ambulatorio. Ha evolucionado estable desde el punto de vista funcional pulmonar.

Adenoid cystic carcinoma of Bartholin glands (BG) is a rare, slow-growing but a highly aggressive tumor with remarkable capacity for local recurrence and distant metastasis. We present the case of a 48 year-old female patient with a history of surgical treatment for right Bartholin abscess. The biopsy showed a cystic adenoid carcinoma of the BG, which led to radical hemivulvectomy and inguinofemoral lymphadenectomy. The biopsy show inguinal lymph node metastasis on 4 of 12 lymph nodes and positive surgical resection margin. Adjuvant radiotherapy was applied. The patient doesnt present to her clinical follow up, and consult three years later with radiological evidence of sacroiliac metástasis on bone scintigraphy. Study was completed with thorax, abdomen and pelvis tomography scan, and showed multiple bilateral lung nodules. The patient was transfered to National Thoracic Institute, and preoperative study was performed. We decide to obtain histologycal confirmation by a video thoracoscopy, it was performed without incidents. Histology show metastasis of adenoid cystic carcinoma pattern, concordant with primary tumor. The patient was submitted to the oncology committee and palliative radiotherapy was indicated for sacroiliac lesion. The patient evolve stable and asintomatic at ambulatory clinical control.

The ROCK Inhibitor Fasudil Prevents Chronic Restraint Stress-Induced Depressive-Like Behaviors and Dendritic Spine Loss in Rat Hippocampus.

Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudil-treated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.

What Do We Really Know About 5-HT1A Receptor Signaling in Neuronal Cells?

Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT1A receptor (5-HT1AR), specially contrasting with those findings obtained in neuronal cells. The 5-HT1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT1AR differs from other 5-HT receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by Gα isoforms and some cascades involve ßγ signaling. The activity of 5-HT1AR usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca2+, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT1AR induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and phosphoinositide-3-kinase (PI3K)-Akt signaling pathways. Advances in understanding the actions of 5-HT1AR and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.

Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons.

Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras-related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin-depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin-binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro-RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR-138 indirectly activates RhoA, and miR-134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR-132 activates RAC1, promoting spine formation. We evaluated whether N-cadherin/ß-catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N-cadherin levels but not ß-catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR-132 or miR-134. Although the stress did not modify the RAC-LIMK-cofilin signaling pathway, we observed increased phospho-MYPT1 levels, probably mediated by RhoA-ROCK activation. Furthermore, chronic stress raises the levels of miR-138 in accordance with the observed activation of the RhoA-ROCK pathway. Our findings suggest that a dysregulation of RhoA-ROCK activity by chronic stress could potentially underlie spine loss in hippocampal neurons.

Avaliação da microdureza do esmalte de dentes decíduos de crianças com paralisia cerebral / Enamel microhardness of primary teeth of cerebral palsy children

Introdução: Em indivíduos com paralisia cerebral, ocorre redução do fluxo salivar, o que pode predispor à hipomineralização do esmalte e à cárie dentária. Objetivo: Comparar a microdureza do esmalte de dentes decíduos anteriores e posteriores de crianças com paralisia cerebral (PC) e crianças normorreativas (NR). Material e Método: Foram utilizados 58 dentes decíduos esfoliados/extraídos, que foram distribuídos em quatro grupos: (A) anteriores de PC (n=14); (B) anteriores de NR (n=16); (C) posteriores de PC (n=14), e (D) posteriores de NR (n=14). Os dentes foram seccionados, incluídos em resina acrílica, lixados e polidos. A análise da microdureza longitudinal foi realizada em microdurômetro com endentador do tipo Knoop, com carga estática de 25 g/f e tempo de 5 segundos. Foram realizadas três fileiras de 12 endentações, distanciadas entre si em 100 mm, com profundidade entre 10 e 180 mm. Foram obtidas as médias de cada profundidade para cada dente e, posteriormente, as médias de cada profundidade para cada grupo avaliado. O teste estatístico empregado foi o de Mann-Whitney (α=5%)). Resultado: As médias de microdureza foram 253,5 ± 55,3 (A), 247,6 ± 45,7 (B), 284,4 ± 68,7 (C) e 252,2 ± 53,8 (D). Não houve diferença estatisticamente significante entre os grupos A e B e os grupos C e D, para cada profundidade e para a média global (p>0,05). Conclusão: Pôde-se concluir que a microdureza de esmalte de dentes decíduos anteriores e posteriores de crianças com PC foi semelhante à microdureza de esmalte de dentes decíduos de crianças normorreativas. .

Introduction: Cerebral palsy subjects present reduced salivary flow, which may predispose to enamel hypomineralization and dental caries. Aim: To compare the enamel microhardness of anterior and posterior primary teeth of normorreactive children (NR) and children with cerebral palsy (CP). Material and Method: The sample was consisted of 58 exfoliated/extracted primary teeth distributed into 4 groups: (A) anterior teeth of CP (n= 14), (B) anterior teeth of NR (n=16),(C) posterior teeth of CP (n=14) and (D) posterior teeth of NR (n=14). The teeth were hemisectioned, embedded in acrylic resin, grounded and polished. The longitudinal microhardness analysis was carried out in a microdurometer with a Knoop indenter with a 25-gram load for 5 seconds. Three rows of 12 indentations were made from the outer surface from 10 to 180 mm. The rows were spaced 100 mm from each other. The values of the three measurements at each distance were averaged for each tooth and, afterwards, for each group. The non-parametric statistical test used was the Mann-Whitney U (α=5%). Result: The microhardness means data were 253.5 ± 55.3 (A), 247.6 ± 45.7 (B), 284.4 ± 68.7 (C) and 252.2 ± 53.8 (D).There was no significant difference between the groups A and B, as well as groups C and D for each distance and global average (p>0.05). Conclusion: It can be concluded that the enamel microhardness of anterior and posterior primary teeth of cerebral palsy children was similar to the normorreactive children. .

Serotonin (5-HT) regulates neurite outgrowth through 5-HT1A and 5-HT7 receptors in cultured hippocampal neurons.

Serotonin (5-HT) production and expression of 5-HT receptors (5-HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5-HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5-HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development. Signalling mediated by the G-protein-coupled 5-HT1A R and 5-HT7 R, however, has been associated with neuronal plasticity. Thus, we hypothesized that 5-HT promotes neurite outgrowth through 5-HT1A R and 5-HT7 R. The involvement of 5-HT1A R and 5-HT7 R in the morphology of rat hippocampal neurons was evaluated by treating primary cultures at 2 days in vitro with 5-HT and specific antagonists for 5-HT1A R and 5-HT7 R (WAY-100635 and SB269970, respectively). The stimulation of hippocampal neurons with 100 nM 5-HT for 24 hr produced no effect on either the number or the length of primary neurites. Nonetheless, after 5HT7 R was blocked, the addition of 5-HT increased the number of primary neurites, suggesting that 5HT7 R could inhibit neuritogenesis. In contrast, 5-HT induced secondary neurite outgrowth, an effect inhibited by 1 µM WAY-100635 or SB269970. These results suggest that both serotonergic receptors participate in secondary neurite outgrowth. We conclude that 5-HT1A R and 5-HT7 R regulate neuronal morphology in primary hippocampal cultures by promoting secondary neurite outgrowth.

Social accountability of medical schools and academic primary care training in Latin America: principles but not practice.

BACKGROUND: Latin America has one of the highest rates of health disparities in the world and is experiencing a steep increase in its number of medical schools. It is not clear if medical school authorities consider social responsibility, defined as the institutional commitment to contribute to the improvement of community well-being, as a priority and if there are any organizational strategies that could reduce health disparities. OBJECTIVE: To study the significance and relevance of social responsibility in the academic training of medical schools in Latin America. METHODS: The study combined a qualitative thematic literature review of three databases with a quantitative design based on a sample of nine Latin American and non-Latin American countries. RESULTS: The thematic analysis showed high agreement among academic groups on considering medical schools as 'moral agents', part of a 'social contract' and with an institutional responsibility to reduce health disparities mainly through the implementation of strong academic primary care programs. The quantitative analysis showed a significant association between higher development of academic primary care programs and lower level of health disparities by country (P = 0.028). However, the data showed that most Latin American medical schools did not prioritize graduate primary care training. CONCLUSIONS: The study shows a discrepancy between the importance given to social responsibility and academic primary care training in Latin America and the practices implemented by medical schools. It highlights the need to refocus medical education policies in the region.

Rinoescleroma / Rhinoscleroma

Paciente masculino de 19 años de edad, proveniente de zona rural, con cuadro clínico de 3 años de oclusión nasal, episodios de inflamación facial, epistaxis, rinorrea fétida, hipoacusia derecha, adenopatías faciales múltiples y axiliares bilaterales; fue referido al Hospital México por una lesión granulomatosa obstructiva del tabique nasal. Una biopsia inicial reveló la presencia de tejido con infiltrado inflamatorio crónico, con predominio de macrófagos de aspectos espumoso. Una segunda biopsia fue positiva por Klebsiella pneumoniae subsp. rhinoscleromatis, y por anatomía patológica se describió una hiperplasia pseudoepiteliomatosa y en lámina propia denso infiltrado inflamatorio con base en linfocitos, células plasmáticas, cuerpos de Russell y macrófagos con citoplasma vacuolado, con presencia de microorganismos y detritos. El paciente recibió terapia con ciprofloxacina vía oral por siete meses, con lo cual resolvió desde el punto de vista etiológico...